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CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene
Abstract
The role of CaMK II in regulating GLUT4 expression in response to intermittent exercise was investigated. Wistar rats completed 5 × 17-min bouts of swimming after receiving 5 mg/kg KN93 (a CaMK II inhibitor), KN92 (an analog of KN93 that does not inhibit CaMK II), or an equivalent volume of vehicle. Triceps muscles that were harvested at 0, 6, or 18 h postexercise were assayed for 1) CaMK II phosphorylation by Western blot, 2) acetylation of histone H3 at the Glut4 MEF2 site by chromatin immunoprecipitation (ChIP) assay, 3) bound MEF2A at the Glut4 MEF2 cis-element by ChIP, and 4) GLUT4 expression by RT-PCR and Western blot. Compared with controls, exercise caused a twofold increase in CaMK II phosphorylation. Immunohistochemical stains indicated increased CaMK II phosphorylation in nuclear and perinuclear regions of the muscle fiber. Acetylation of histone H3 in the region surrounding the MEF2 binding site on the Glut4 gene and the amount of MEF2A that bind to the site increased approximately twofold postexercise. GLUT4 mRNA and protein increased ∼2.2- and 1.8-fold, respectively, after exercise. The exercise-induced increases in CaMK II phosphorylation, histone H3 acetylation, MEF2A binding, and GLUT4 expression were attenuated or abolished when KN93 was administered to rats prior to exercise. KN92 did not affect the increases in pCaMK II and GLUT4. These data support the hypothesis that CaMK II activation by exercise increases GLUT4 expression via increased accessibility of MEF2A to its cis-element on the gene.
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“Active CaMK can increase both the capacity for glucose uptake through upregulation of the glucose transporter GLUT4 [31]”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [31]
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“Ca /calmodulindependent protein kinase (CaMK) also seems to modulate MEF2 activity via histone acetylation in response to acute exercise (74).”
BackgroundNitert, M. D., Dayeh, T., Volkov, P., Elgzyri, T., Hall, E., Nilsson, E., Yang, B. T., Lang, S., Parikh, H. M., Wessman, Y., et al. (2012) · Diabetes · doi:10.2337/db11-1653 · Cited by 422
Yan, Z., Okutsu, M., Akhtar, Y., & Lira, V. A. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00993.2010 · Cited by 354
Metadata
- Authors
- Smith, J. A. H., Kohn, T. A., Chetty, A. K., & Ojuka, E. O.
- Affiliations
- University of Cape Town (ZA)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-09
- Volume
- 295
- Issue
- 3
- Pages
- E698-E704
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2165038103
- Cited by
- 115
- References
- 46
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 10 · 2019: 10 · 2018: 5 · 2017: 9 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 11 · 2012: 6
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- CaMKII, GLUT4, MEF2A, histone H3 acetylation, physical activity, muscle gene expression, KN-93, triceps brachii, transcriptional regulation, swimming training
- MeSH terms
- Acetylation, Animals, DNA, Enzyme Activation, Histones, Male, Phosphorylation, Physical Conditioning, Animal, Protein Binding, Blotting, Western, Rats, Wistar, Myogenic Regulatory Factors, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, MADS Domain Proteins, Glucose Transporter Type 4, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, MEF2 Transcription Factors
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